Maliszewski C R, Sato T A, Vanden Bos T, Waugh S, Dower S K, Slack J, Beckmann M P, Grabstein K H
Department of Immunology, Immunex Corporation, Seattle, WA 98101.
J Immunol. 1990 Apr 15;144(8):3028-33.
IL-1 and IL-4 are important mediators of B cell growth and differentiation. The cell-surface receptors for these cytokines have recently been cloned and recombinant soluble receptors have been produced that bind their respective ligand. The ability of soluble forms of the murine IL-1R (sIL-1R) and IL-4R (sIL-4R) to inhibit B cell functions in vitro was examined. Proliferation of B cells treated with anti-Ig plus IL-1 or IL-4 was inhibited by the appropriate soluble receptor. sIL-4R also inhibited IL-4-dependent B cell differentiation as measured by: induction of IgG1 and IgE secretion by LPS blasts, down-regulation of IgG3 secretion by LPS blasts, increased Ia expression, and increased Fc epsilon R (CD23) expression. The inhibitory effects of the soluble receptors were found to be highly specific in that sIL-4R had no effect on IL-1-induced B cell activity and sIL-1R had no effect on IL-4 activity, further demonstrating the existence of two independent pathways of B cell activation directed by IL-1 and IL-4.
白细胞介素-1(IL-1)和白细胞介素-4(IL-4)是B细胞生长和分化的重要介质。这些细胞因子的细胞表面受体最近已被克隆出来,并且已经产生了能结合各自配体的重组可溶性受体。研究了小鼠白细胞介素-1受体(sIL-1R)和白细胞介素-4受体(sIL-4R)的可溶性形式在体外抑制B细胞功能的能力。用抗免疫球蛋白加IL-1或IL-4处理的B细胞增殖受到相应可溶性受体的抑制。sIL-4R还抑制了IL-4依赖的B细胞分化,这通过以下指标来衡量:脂多糖刺激的细胞分泌IgG1和IgE、脂多糖刺激的细胞下调IgG3分泌、增加Ia表达以及增加FcεR(CD23)表达。发现可溶性受体的抑制作用具有高度特异性,因为sIL-4R对IL-1诱导的B细胞活性没有影响,而sIL-1R对IL-4活性没有影响,这进一步证明了由IL-1和IL-4介导的两条独立的B细胞激活途径的存在。